Upadacitinib in Patients with Psoriatic Arthritis and Inadequate Response to Biologics: 56-Week Data from the Randomized Controlled Phase 3 SELECT-PsA 2 Study

Abstract

Introduction: Upadacitinib is a Janus kinase inhibitor under investigation in patients with psoriatic arthritis (PsA). This study assessed the 56-week efficacy and safety of upadacitinib in patients with PsA and an inadequate response or intolerance to biologic therapy.

Methods: In the phase 3 SELECT-PsA 2 study, patients were randomized to 56 weeks of blinded treatment with oral upadacitinib 15 or 30 mg once daily, or placebo switched to upadacitinib 15 or 30 mg once daily at week 24. Efficacy endpoints included the proportion of patients achieving 20/50/70% improvement in American College of Rheumatology criteria (ACR20/50/70), 75/90/100% improvement in Psoriasis Area and Severity Index (PASI75/90/100), and minimal disease activity. Safety was assessed throughout the study.

Results: Of 641 patients who received ≥ 1 dose of study drug, 479 (74.7%) completed 56 weeks of treatment. Improvements in the proportion of patients achieving ACR20/50/70, PASI75/90/100, and minimal disease activity were maintained with both doses of upadacitinib through 56 weeks. Week 56 results for patients who switched from placebo to upadacitinib at week 24 were similar to those for patients originally randomized to the upadacitinib groups. The exposure-adjusted event rate for serious infections was 2.6 and 6.1 events/100 patient-years in the upadacitinib 15 and 30 mg groups, respectively. Herpes zoster occurred more frequently with upadacitinib 30 versus 15 mg; most cases were non-serious.

Conclusion: In patients with PsA who had an inadequate response or intolerance to biologic therapy, the efficacy of upadacitinib was maintained over 56 weeks with no new significant safety signals observed.

Trial registration: NCT03104374.

Keywords: Janus kinase inhibitors; Psoriatic arthritis; Upadacitinib.

Figures

Fig. 1

Patient disposition at week 56. aOne patient did not receive study drug. AE adverse event, PBO placebo, QD once daily, UPA upadacitinib

Fig. 2

Patients achieving a ACR20, b ACR50, and c ACR70 over 56 weeks (non-responder imputation). The gray dotted line represents PBO prior to patients switching to UPA. ACR20/50/70 American College of Rheumatology criteria 20/50/70% improvement, CI confidence interval

Fig. 3

Patients achieving minimal disease activity over 56 weeks (non-responder imputation). The gray dotted line represents PBO prior to patients switching to UPA. MDA minimal disease activity

Fig. 4

Patients achieving a PASI75, b PASI90, c PASI100, and d sIGA 0 or 1 and  ≥ 2-point improvement from baseline over 56 weeks (non-responder imputation). The gray dotted line represents PBO prior to patients switching to UPA. PASI75/90/100 75/90/100% improvement in Psoriasis Area and Severity Index, sIGA Static Investigator’s Global Assessment

Fig. 5

a EAERs and b EAIRs of treatment-emergent adverse events through week 56. a Excluding tuberculosis and herpes zoster. b Four cases of basal cell carcinoma and 1 case of squamous cell carcinoma of the skin in the UPA 15 mg group. c Three cases of basal cell carcinoma and 3 cases of squamous cell carcinoma of the skin in the UPA 30 mg group. d Two cases of prostate cancer and single cases of malignant melanoma, ovarian cancer, and rectal cancer in the UPA 15 mg group. e Single cases of basosquamous carcinoma (considered NMSC after medical review), malignant melanoma, oropharyngeal squamous cell carcinoma, and rectal adenocarcinoma, as well as endometrial cancer and ovarian cancer (occurred in the same patient), in the UPA 30 mg group. f Two events of treatment-emergent abnormal lymphocyte morphology were identified in the UPA 15 mg group; abnormal lymphocytes were not reported in subsequent laboratory testing. CPK Creatine phosphokinase, E/100 PY events per 100 patient-years, EAIR exposure-adjusted incidence rate, EAER exposure-adjusted event rate, GI gastrointestinal, MACE major adverse cardiovascular event (defined as non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death), n/100 PY number per 100 patient-years, NMSC non-melanoma skin cancer, PY patient-year, VTE venous thromboembolic event (defined as deep vein thrombosis or pulmonary embolism)